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排序方式: 共有108条查询结果,搜索用时 46 毫秒
41.
Hoepping A Diekers M Deuther-Conrad W Scheunemann M Fischer S Hiller A Wegner F Steinbach J Brust P 《Bioorganic & medicinal chemistry》2008,16(3):1184-1194
Neuroimaging of GABA(A) receptors offers the potential for a better diagnosis of diseases related to a dysfunction of the GABAergic neurotransmission. A series of potent fluorinated analogues of the pyrazolopyrimidine Indiplon has been synthesized and evaluated in vitro as potential agents for imaging the GABA(A) receptor by means of positron emission tomography (PET). The most promising compound N-(3-fluoropropyl)-N-[3-[3-(thiophene-2-carbonyl)-pyrazolo[1,5-a]pyrimidin-7-yl]-phenyl]-acetamide (5b) showed an IC(50) value of 2.78+/-0.63 nM comparable to the lead compound Indiplon (IC(50) 3.29+/-0.37 nM), thus making it an interesting candidate for further investigations. In addition to the fluorinated reference compounds, suitable precursors for (18)F-radiolabelling studies have been synthesized. 相似文献
42.
Jessica Jüppner Umarah Mubeen Andrea Leisse Camila Caldana Henrike Brust Martin Steup Marion Herrmann Dirk Steinhauser Patrick Giavalisco 《The Plant journal : for cell and molecular biology》2017,92(2):331-343
Metabolites and lipids are the final products of enzymatic processes, distinguishing the different cellular functions and activities of single cells or whole tissues. Understanding these cellular functions within a well‐established model system requires a systemic collection of molecular and physiological information. In the current report, the green alga Chlamydomonas reinhardtii was selected to establish a comprehensive workflow for the detailed multi‐omics analysis of a synchronously growing cell culture system. After implementation and benchmarking of the synchronous cell culture, a two‐phase extraction method was adopted for the analysis of proteins, lipids, metabolites and starch from a single sample aliquot of as little as 10–15 million Chlamydomonas cells. In a proof of concept study, primary metabolites and lipids were sampled throughout the diurnal cell cycle. The results of these time‐resolved measurements showed that single compounds were not only coordinated with each other in different pathways, but that these complex metabolic signatures have the potential to be used as biomarkers of various cellular processes. Taken together, the developed workflow, including the synchronized growth of the photoautotrophic cell culture, in combination with comprehensive extraction methods and detailed metabolic phenotyping has the potential for use in in‐depth analysis of complex cellular processes, providing essential information for the understanding of complex biological systems. 相似文献
43.
Structure and Functional Characterization of a Novel Human Low-Voltage
Activated Calcium Channel 总被引:7,自引:0,他引:7
Mark E. Williams Mark S. Washburn Michael Hans Arturo Urrutia Paul F. Brust Patricia Prodanovich Michael M. Harpold & Kenneth A. Stauderman 《Journal of neurochemistry》1999,72(2):791-799
Abstract : We have isolated and characterized overlapping cDNAs encoding a novel, voltage-gated Ca2+ channel α1 subunit, α1H , from a human medullary thyroid carcinoma cell line. The α1H subunit is structurally similar to previously described α1 subunits. Northern blot analysis indicates that α1H mRNA is expressed throughout the brain, primarily in the amygdala, caudate nucleus, and putamen, as well as in several nonneuronal tissues, with relatively high levels in the liver, kidney, and heart. Ba2+ currents recorded from human embryonic kidney 293 cells transiently expressing α1H activated at relatively hyperpolarized potentials (-50 mV), rapidly inactivated (τ = 17 ms), and slowly deactivated. Similar results were observed in Xenopus oocytes expressing α1H . Singlechannel measurements in human embryonic kidney 293 cells revealed a single-channel conductance of ~9 pS. These channels are blocked by Ni2+ (IC50 = 6.6 μ M ) and the T-type channel antagonists mibefradil (~50% block at 1 μ M ) and amiloride (IC50 = 167 μ M ). Thus, α1H -containing channels exhibit biophysical and pharmacological properties characteristic of low voltage-activated, or T-type, Ca2+ channels. 相似文献
44.
45.
Monoclonal antibodies against chicken type V collagen: production, specificity, and use for immunocytochemical localization in embryonic cornea and other organs 总被引:23,自引:17,他引:6
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TF Linsenmayer JM Fitch TM Schmid Zak NB E Gibney RD Sanderson R Mayne 《The Journal of cell biology》1983,96(1):124-132
Two monoclonal antibodies have been produced against chick type V collagen and shown to be highly specific for separate, conformational dependent determinants within this molecule. When used for immunocytochemical tissue localization, these antibodies show that a major site for the in situ deposition of type V is within the extracellular matrices of many dense connective tissues. In these, however, it is largely in a form unavailable to the antibodies, thus requiring a specific “unmasking” treatment to obtain successful immunocytochemical staining. The specificity of these two IgG antibodies was determined by inhibition ELISA, in which only type V and no other known collagen shows inhibition. In ELISA, mixtures of the two antibodies give an additive binding reaction to the collagen, suggesting that each is against a different antigenic determinant. That both antigenic determinants are conformational dependent, being either in, or closely associated with, the collagen helix is demonstrated by the loss of antibody binding to molecules that have been thermally denatured. The temperature at which this occurs, as assayed by inhibition ELISA, is very similar to that at which the collagen helix melts, as determined by optical rotation. This gives strong additional evidence that the antibodies are directed against the collagen. The antibodies were used for indirect immunofluorescence analyses of cryostat sections of corneas and other organs from 17 to 18-day-old chick embryos. Of all tissues examined only Bowman’s membrane gave a strong staining reaction with cryostat sections of unfixed material. Staining in other areas of the cornea and in other tissues was very light or nonexistent. When, however, sections were pretreated with pepsin dissolved in dilute HAc or, surprisingly, with the dilute HAc itself dramatic new staining by the antibodies was observed in most tissues examined. The staining, which was specific for the anti-type V collagen antibodies, was largely confined to extracellular matrices of dense connective tissues. Experiments using protease inhibitors suggested that the “unmasking” did not involve proteolysis. We do not yet know the mechanism of this unmasking; however, one possibility is that the dilute acid causes swelling or conformational changes in a type-V collagen-containing supramolecular structure. Further studies should allow us to determine whether this is the case. 相似文献
46.
This paper is a report about a rotation-viscometer with a submerged rotor which has been developed for measuring the viscosity of biological macromolecules. The device avids the effects of surface disturbance. The rotor is centered and height-balanced electromagnetically and is controlled by a light barrier. The driving force is rotating electromagnetic field and rotor revolution periods are measured by an electronic timer controlled by a second light barrier. Shearing effects are negligible if very slow revolution are pre-selected; thus, intrinsic viscosity for DNA can be obtained by merely extrapolating the concentration dependence. In contrast to DNA, chromatin has a very low viscosity with almost no dependence on concentration. If the ionic strength of a chromatin solution is decreased, the viscosity increases due to structural unfolding. 相似文献
47.
Expression of the lacZ gene from two methanol-regulated promoters in Pichia pastoris. 总被引:14,自引:0,他引:14
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J F Tschopp P F Brust J M Cregg C A Stillman T R Gingeras 《Nucleic acids research》1987,15(9):3859-3876
Two DNA fragments containing putative control regions regulating the expression of the alcohol oxidase (AOX) and dihydroxy-acetone synthase (DAS) genes from the methylotrophic yeast Pichia pastoris were used in the construction of vectors for the expression of the Escherichia coli lacZ gene. These vectors were transformed into P. pastoris host cells and employed in experiments to measure the control mechanisms employed by each promoter in the production of beta-galactosidase fusion products. Results in P. pastoris suggest that the processes used to regulate the expression of these gene fusions involve both repression/derepression and induction mechanisms. Expression of the AOX-lacZ and DAS-lacZ fusions was examined in Saccharomyces cerevisiae as well. Interestingly, beta-galactosidase was expressed in a regulated manner in the heterologous host. 相似文献
48.
Rodrigo Teodoro Matthias Scheunemann Barbara Wenzel Dan Peters Winnie Deuther-Conrad Peter Brust 《Bioorganic & medicinal chemistry letters》2018,28(9):1471-1475
By structure–activity relationship studies on the tilorone scaffold, the ‘one armed’ substituted dibenzothiophenes and the fluoren-9-ones were identified as the most potential α7 nAChR ligands. While the suitability of dibenzothiophene derivatives as PET tracers is recognized, the potential of fluoren-9-ones is insufficiently investigated. We herein report on a series of fluoren-9-one based derivatives targeting α7 nAChR with compounds 8a and 8c possessing the highest affinity and selectivity. Accordingly, with [18F]8a and [18F]8c we designed and initially evaluated the first fluoren-9-one derived α7 nAChR selective PET ligands. A future application of these radioligands is facilitated by the herein presented successful implementation of fully automated radiosynthesis. 相似文献
49.
50.
Noncoding RNAs have recently been identified as essential components of the nuclear suborganelles called paraspeckles. This finding will facilitate our understanding of the molecular dynamics and physiological role of these enigmatic macromolecular structures. 相似文献